Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity.
R Feio-Azevedo, V M Costa, D J Barbosa, A Teixeira-Gomes, I Pita, S Gomes, F C Pereira, M Duarte-Araújo, J A Duarte, F Marques, Eduarda Fernandes, Maria L Bastos, F Carvalho, J P Capela
Archives of Toxicology July 2018 DOI: 10.1007/s00204-018-2226-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent (post-natal day 40) and aged (mean 20 months old) Wistar rats |
| Intervention | MDMA |
| Dose | Adolescents: 3 × 5 mg/kg, 2 h apart; aged: 2 × 5 mg/kg, 2 h apart, intraperitoneally |
| Duration | Animals were killed 7 days after MDMA administration |
| Topics | MDMA |
| Keywords | Aged rats Cardiotoxicity Nephrotoxicity Neurotoxicity Tau “ecstasy” |
| Key findings | Age determined the pattern of MDMA toxicity in rats: aged animals showed hippocampal serotonergic neurotoxicity and increased p-Tau that adolescents did not, and aged animals had greater heart and kidney tissue damage, while both age groups developed liver fibrosis. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats received MDMA intraperitoneally. Animals were killed 7 days later, and the frontal cortex, hippocampus, striatum and cerebellum brain areas were dissected, and heart, liver and kidneys were collected. MDMA caused hyperthermia in both treated groups, but aged rats had a more dramatic temperature elevation. MDMA promoted serotonergic neurotoxicity only in the hippocampus of aged, but not in the adolescents' brain, and did not change the levels of dopamine or serotonin metabolite in the striatum of both groups. Differential responses according to age were also seen regarding brain p-Tau levels, a hallmark of a degenerative brain, since only aged animals had significant increases. MDMA evoked brain oxidative stress in the hippocampus and striatum of aged, and in the hippocampus, frontal cortex, and striatum brain areas of adolescents according to protein carbonylation, but only decreased GSH levels in the hippocampus of aged animals. The brain maturational stage seems crucial for MDMA-evoked serotonergic neurotoxicity. Aged animals were more susceptible to MDMA-induced tissue damage in the heart and kidneys, and both ages had an increase in liver fibrotic tissue content. In conclusion, age is a determinant factor for the toxic events promoted by "ecstasy". This work demonstrated special susceptibility of aged hippocampus to MDMA neurotoxicity, as well as impressive damage to the heart and kidney tissue following "ecstasy".
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 7
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- Use and abuse of dissociative and psychedelic drugs in adolescence Pharmacology, Biochemistry, and Behavior January 27, 2021
- Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms. European Journal of Pharmacology May 7, 2021
- MDMA-assisted psychotherapy for PTSD in adolescents: rationale, potential, risks, and considerations. European Child & Adolescent Psychiatry November 1, 2024
- A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA) Current Research in Toxicology May 27, 2022
and 2 more in the library
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